Association of prior Angiotensin receptor-neprilysin inhibitor use with the initial eGFR dip after initiation of SGLT2 inhibitors in patients with chronic kidney disease.

BACKGROUND

Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection; however, a transient decline in estimated glomerular filtration rate (eGFR), known as the ''initial dip'', is frequently observed after initiation. Although this phenomenon reflects changes in intraglomerular hemodynamics, excessive decline may be associated with worsening renal function. Angiotensin receptor-neprilysin inhibitors (ARNIs) have demonstrated renal protective effects in heart failure, but their impact on the initial dip after SGLT2 inhibitor initiation remains unclear.

METHODS

We retrospectively evaluated the effect of prior ARNI use on the initial dip following SGLT2 inhibitor initiation in 157 patients with chronic kidney disease who newly started SGLT2 inhibitors between 2022 and 2025. Patients were classified into an ARNI group and an angiotensin receptor blocker (ARB) group. The primary outcome was the incidence of an initial dip, defined as a ≥ 5% decline in eGFR after SGLT2 inhibitor initiation. The secondary outcome was the change in eGFR and urine protein excretion at 1 year.

RESULTS

The incidence of the initial dip did not significantly differ between the ARNI and ARB groups (30.0% vs. 46.5%, p = 0.10). However, multivariate logistic regression analysis showed that prior ARNI use was independently associated with a lower risk of initial dip (odds ratio 0.30, 95% CI 0.10-0.89, p = 0.02). Prior ARNI use was not significantly associated with longitudinal eGFR and urine protein changes at 1 year.

CONCLUSIONS

Prior ARNI use was associated with a lower risk of the initial eGFR dip following SGLT2 inhibitor initiation, although prospective studies are needed to confirm these findings.